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Background: The intramedullary nailing of a femoral shaft metastatic fracture or an impending fracture has been complicated by hemodynamic accidents in up to 13% of patients. In previous studies, otherwise healthy patients pulled well through the nailing despite high pulmonary shunting and vascular tone and right ventricular strain. We hypothesized that unfavorable hemodynamic and oxygenation trends milder than catastrophic ones can be found intraoperatively in most patients with a pathological fracture and cancer-affected lungs., Methods: Eleven patients with a femoral metastatic fracture or an impending fracture were studied in general anesthesia. Radial artery and fast-response pulmonary artery catheters were inserted. Pre-, intra-, and postoperatively, 26 variables were measured and/or calculated up to 20 hours. Reamed nailing with a gamma nail was performed., Results: At awake baseline, the mean pulmonary arterial pressure was 20 mm Hg ± 7 mm Hg and the shunt flow was 19% ± 6%. As response to the nailing, shunting increased from 14% ± 7% (mechanically ventilated) to 23% ± 10% (p < 0.05), and mean pulmonary arterial pressure increased to 29 mm Hg ± 6 mm Hg (p < 0.001). Oxygenation deteriorated to a level typical of acute lung injuries (Pao2/FIO2 242 mm Hg ± 73 mm Hg; p < 0.05). Intraoperatively, the oxygen delivery was poor, and acidosis developed (base excess, -2.9, p < 0.05)., Conclusion: The baseline condition of patients with a pathological femoral fracture was comparable with that of healthy patients subjected to femoral fracture surgery. After reaming, arterial oxygenation deteriorated, being clinically poor for the rest of the study. We suggest increased inspiratory oxygen concentration intra- and postoperatively and maintenance of oxygen delivery by transfusions as needed, especially because hypoxia stimulates the growth of cancer.

Mammographic screening is associated with a reduced risk of breast cancer recurrence. The objective of the study was to evaluate treatment costs due to breast cancer recurrence in relation to patients' use of mammographic screening, consecutively collected in a defined population. The study included 418 women exposed to screening and 109 women unexposed to screening diagnosed with stage I-III breast cancer. During the first eight years after primary diagnosis, 19% (N=80) of the exposed women and 33% (N=36) of the unexposed women developed recurrent disease, P=0.002. In the exposed group, 41% of the 8-year treatment costs were for the treatment of patients who developed recurrent disease, compared with 52% in the unexposed group, P=0.039. Among the relapsed patients, the mean post-recurrence costs were EUR14,950, accounting for 65% of their total 8-year costs. The mean post-recurrence costs were comparable for both exposure groups irrespective of the detection method.

Aims: The aim was to assess the effect of population-based mammography screening on treatment costs for fatal breast cancer in Turku, Finland., Materials and Methods: The study included 556 women with invasive breast cancer, diagnosed at the age of 40-74 years in 1987-1993: 427 in the screened group (screen-detected or interval cancer) and 129 in the unscreened group (not yet invited or refused screening). Both groups were followed up for 8 years from diagnosis., Results: In the unscreened group, 32 (25%) patients died of breast cancer versus 49 (12%) in the screened group (p < 0.001). The non-discounted mean treatment costs were 2.8-fold for those dying of breast cancer compared to survivors: 26,222 euros versus 9,434 euros; the difference between means was 16,788 euros (95% CI 14,915-18,660) (p<0.001). The mean costs for fatal cases were high, irrespective of the way cancer was detected: 23,800 euros in the unscreened group versus 27,803 euros in the screened group; the difference between means was -4,003 euros (-10,810 to 2802) (p=0.245). In the unscreened group, patients with fatal breast cancer accounted for 41% (0.76/1.87 million euros) of the total treatment costs versus 29% (1.36/4.76 million euros) in the screened group. It was estimated that about one third of costs for fatal breast cancer were avoided through mammography screening, accounting for 72-81% of the estimated total treatment cost savings achieved by screening. About 31-35% of the screening costs for 1987 to 1993 were offset by savings in treatment costs., Conclusions: Treatment costs for fatal breast cancer are high. Mammography screening results in substantial treatment cost savings, in which reduction of fatal disease is the key element.

Background: The current report is a long-term evaluation of breast carcinoma recurrence, factors predicting recurrence, and postrecurrence prognosis in relation to patients' use of service screening, which has been provided in Turku, Finland, since 1987 for women ages 40-74 years., Methods: The current study included 527 invasive breast carcinomas: 418 in the screening group (which included screen-detected and interval malignancies) and 109 in the nonscreening group (which included breast carcinomas detected before initial screening and those detected in patients who chose not to undergo screening). These breast carcinomas were diagnosed among women ages 40-74 years between 1987 and 1993, with follow-up extending until the end of 2001., Results: In the screening group, the risk of recurrence was only approximately half of the corresponding risk in the nonscreening group (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.39-0.83; P = 0.003). Five years after the primary diagnosis, 16% of patients in the screening group and 28% of patients in the nonscreening group (P = 0.001) had experienced recurrence; 10 years after diagnosis, the corresponding rates were 21% and 34%, respectively (P = 0.001). Postrecurrence prognosis was comparable for both detection groups (HR, 1.17; 95% CI, 0.70-1.94; P = 0.551), with approximately half of all patients dying of disease 5 years after recurrence. Detection of breast carcinoma via a method other than mammographic screening was associated with a high risk of recurrence on univariate analysis. On Cox multivariate analysis, risk factors for recurrence included lobular histologic type (HR, 2.23; 95% CI, 1.44-3.48; P < 0.001), poor histologic grade (HR, 2.02; 95% CI, 1.20-3.39; P = 0.008), and large tumor size (HR, 1.60; 95% CI, 1.07-2.37; P = 0.021)., Conclusions: Long-term data from a population-based program demonstrated that mammographic screening reduced patients' risk of breast carcinoma recurrence. Specifically, the risk for patients with screen-detected disease was only approximately half of the risk for patients with non-screen-detected disease. Nonetheless, postrecurrence prognosis was comparable for patients in both detection groups., ((c) 2004 American Cancer Society)

Background: The objective of this study was to evaluate the hospital treatment costs of invasive breast cancer in relation to the mode of detection, i.e. by mammography screening, between screenings or without screening during a population-based mammography screening programme, which started in 1987 among 36,000 women aged 40 to 74 years in the city of Turku, Southwest Finland., Methods: The treatment costs and survival days of 556 women diagnosed with invasive breast cancer at the age of 40 to 74 years in 1987 to 1993 were followed up for five years from diagnosis or until death, whichever occurred first., Results: Screen-detected cancers had the lowest average costs. The mean treatment costs per patient were 1.4-fold for clinical cancers and 1.3-fold for interval cancers compared to screen-detected cancers (p<0.001). The corresponding ratios in the mean treatment costs per survival day were 3.5 for clinical cancers and 1.9 for interval cancers (p<0.001). The mean treatment costs per patient were 1.3-fold for the non-screened group (clinical cancers) compared to the screened group (screen-detected and interval cancers) (p<0.001). The corresponding ratio was 3, when the mean treatment costs per survival day were compared (p<0.001). The estimated savings resulting from early treatment were 26-30% measured as a proportion of the screening costs for 1987 to 1993., Conclusion: The treatment costs of screen-detected cancers are lower than those of cancers detected by other methods. The study shows the potential for reducing treatment costs through early detection of breast cancer by mammography screening.

The purpose of this study was to evaluate the effect of population-based mammography screening on survival. A total of 176 908 screening examinations were performed in 36 000 women aged 40-74 during the years 1987-1997. Screen-detected and interval primary invasive breast cancers (n=685, screened) were more often smaller (P<0.0001), localised (P<0.0001) and histologically better differentiated (grade I vs II-III, P<0.0001) than pre-screening cancers and cancers detected after the defined interval from the last screening (n=184, clinical). Survival was far better in the "screened" group than in the "clinical" group (P<0.0001, HR 2.55; CI 95% 1.77-3.67). Cox's multivariate analysis revealed axillary lymph node negativity (P<0.0001), histological grade I (P=0.0005) and size less than or equal to 20mm (P=0.0118) as explanations of the beneficial effect of screening. A new observation we recorded was that screening had a beneficial effect even in women whose cancer had already spread into the axillary lymph nodes.

Background: The activity of cyclooxygenase-2 (COX-2) is increased in inflammation and in several cancer types. We investigated the expression of COX-2, cyclooxygenase-1 (COX-1), nitric oxide synthase-2 (NOS-2) and nitric oxide synthase-3 (NOS-3) in normal proliferative and secretory human endometrium, and in endometrial adenocarcinoma., Methods: Human endometrium was collected at hysterectomy. Seven samples were in proliferative and 11 samples in secretory stage. Twelve specimens from endometrial carcinoma were collected, as well. Immunohistochemistry was used to investigate the expression of COX-1, COX-2, NOS-2 and NOS-3., Results: COX-2 immunostaining was detected in most specimens of normal proliferative glandular epithelium (86%) and of endometrial carcinomas (92%). COX-2 staining was often detected in cancer cells on the border areas of the tumour and on the areas of invasive growth. Staining for COX-2 was seen in proliferative glands usually only in the basal layer of the endometrium. NOS-2 was usually absent or negligible in proliferative endometrial glands and also in the cancer cells of endometrial adenocarcinomas. No staining for either COX-2 or NOS-2 was seen in specimens of secretory glandular epithelium. The expression of the constitutive COX-1 and NOS-3 was negligible or weak in the glandular epithelium of proliferative and secretory endometrium and in endometrial cancer cells., Conclusions: The expression of the inducible COX-2 but not of COX-1 is stimulated in the glandular epithelium of proliferative endometrium and in the cancer cells of human endometrial adenocarcinoma, in particular in those in the borders of carcinoma and spreading into lymphatic vessels.

Unlabelled: The aim of this prospective study was to investigate if high uptake of 18F-fluoro-2-deoxy-D-glucose (FDG) is associated with aggressiveness in head and neck cancer and low probability of survival., Methods: Thirty-seven patients with squamous-cell carcinoma of the head and neck underwent FDG-PET in the fasting state before cancer treatment. FDG uptake in primary tumor was quantitated as the standardized uptake value of FDG normalized to the predicted lean body mass (SUVlean, n = 37) and as the graphically determined metabolic rate for FDG (rMR[FDG], n = 34). Paraffin-embedded tumor samples were used for histologic evaluation, and expression of cytokeratin and Ki-67 antigen were assessed by immunohistochemistry., Results: Interobserver agreement for the determination of quantitative uptake of FDG in tumors was excellent (r2 = 0.996, p < 0.00001), and all 37 primary tumors were visualized. A high uptake of FDG as assessed by SUVlean was associated with a higher than the median mitotic count (p = 0.01), absence of keratinization (p = 0.03), low or moderate histological grade of differentiation (p = 0.046) and advanced stage (p = 0.03), but not with Ki-67 expression (p = 0.11). The overall survival of patients with a SUVlean lower than or equal to the median value (9.0) was clearly better in univariate analysis than that of patients with a SUVlean higher than the median (3-yr survival 73% versus 22%, relative risk of death (RR) 4.2, 1.6-11.0). However, in a multivariate analysis the only independent predictors of survival were the mitotic count (RR 4.0, 1.4-11.7) and stage (3.8, 1.2-12.2)., Conclusion: High uptake of FDG in untreated head and neck cancer is associated with advanced disease, and may portend poor survival. Aggressive treatment approaches should be considered for patients presenting with a tumor with high uptake of FDG.

Objective: Since the assessment of lymph node metastases in head and neck cancer patients remains a major problem, the findings of different imaging methods and the role of these methods in the clinical management are compared., Material and Methods: Palpation, computed tomography (CT) and low field magnetic resonance imaging (MRI; 0.1 T) are evaluated and compared with ultrasound-guided fine-needle aspiration cytology (US-guided FNAC) prospectively in 105 consecutive patients with a primary cancer in the head and neck region., Results: In the subgroup of 86 patients with palpable normal necks, CT showed lymph nodes fulfilling the radiologic criteria for malignancy in 27% (23/86), MRI in 17% (10/60) and US in 14% (12/86) of the patients US guided FNAC usually showed malignancy in necks containing lymph nodes with central necrosis on CT, but the enlarged lymph nodes that were also common on the contralateral side were often benign on cytology. In 5 patients, FNAC under US-guidance showed malignancy although none of them had lymph nodes fulfilling the radiologic criteria for malignancy. In the other subgroup of 19 patients with palpable metastatic necks, 2 patients had bilateral metastases detected by all imaging methods but not by palpation., Conclusion: CT is superior to low field MRI in depicting small pathologic lymph nodes. Unlike lymph node structure, lymph node size is not a highly reliable criterion for malignancy. The findings must be correlated in relation to the primary disease. Since FNAC under US-guidance offers additional information about enlarged lymph nodes and since it can show malignancy in small lymph nodes not found by other methods, it can be recommended for most head and neck cancer patients irrespective of the use of CT or MRI.

Vaginal PAP smear is frequently used for the follow-up of cervical carcinoma after primary therapy. Irradiation induced atypia can interfere with cytological analysis and thus detection of a local recurrence, or simulate malignant atypia and cause unnecessary suspicion of recurrence. In this retrospective study we evaluated the reliability of cytological analysis and the reported frequency of irradiation induced atypia after radiotherapy. Eighty-nine patients treated for cervical carcinoma at Turku University Central Hospital during the years 1970-88 were included in the study. During the median follow-up of 34 months a total of 697 PAP smears were taken with a median of 7.8 samples per patient. During the follow-up 44 (50%) patients had a recurrent disease, which was local in 17 (39%) cases. Nine out of 12 PAP smears taken 0-60 days before detection of a local recurrence showed class III-V cellular atypia. However, three PAP smears showed class I-II, and were therefore false negative. The rate of false positive samples was only 3%. In 567 PAP smears irradiation induced atypia was indicated as present/not present (+/-) and it was positive in 89 (16%) samples. The detection rate was considerably higher (75%) in class II samples than in rest of the material. Irradiation induced atypia was detected in 28% of the PAP smears taken during the first four months after radiotherapy and the rate decreased thereafter. Cytological analysis of vaginal PAP smear was a reliable indicator of recurrence in most cases and is a valuable tool for the detection of local recurrence of cervical carcinoma after primary radiotherapy.

Background: Lymph node status of the neck is the most important prognostic factor in head and neck cancer patients. Assessment of the lymph nodes status is still often based on palpation only, although the low accuracy of palpation is known., Methods: Altogether 105 consecutive head and neck cancer patients were examined using ultrasound (US) and ultrasound-guided fine-needle aspiration cytology (FNAC) to evaluate the additional information obtained by these methods., Results: Of the 86 patients with palpable normal necks, FNAC taken under US-guidance showed malignancy in 13. The US size criteria for malignancy were fulfilled in 7 of these patients, whereas the lymph nodes were of normal size in 6 of them. In the whole patient material, US-guided FNAC showed bilateral metastasis in 3 patients although only unilateral or no metastasis was found by palpation., Conclusion: US combined with US-guided FNAC can be recommended as a method for evaluating for regional metastases in head and neck cancer patients, both for those with and those without palpable metastasis.

The usefulness of fine-needle aspiration biopsy (FNAB) in the diagnosis and treatment of salivary gland lesions is still controversial. The 438 FNABs taken at the Turku University Central Hospital between 1984-1991 were reviewed. Of these FNABs, 218 had been confirmed histologically. Within this subset, 136 FNABs were taken from benign neoplasms, and of these, 103 were correct (sensitivity 76%, specificity 83%). Only 26 of the 47 FNABs from malignant lesions were cytologically considered to be malignant (sensitivity 55%) and 11 samples raised a false suspicion of malignancy (specificity 92%). Out of 35 FNABs from non-neoplastic lesions, 27 were correct (sensitivity 77%, specificity 80%). There were 175 patients (217 FNABs), who had not been operated on: the follow-up of these patients showed that false malignant and false benign findings were rare. FNAB was safe and no serious complications occurred. However, there was a delay in the treatment of six patients probably because of the physicians' limited understanding of the diagnostic role of FNAB. FNAB offers valuable information about the type of parotid lesion, but the clinician must know how to interpret the cytologic statement, and the decision to use operative and other treatment should not be based solely on the result of FNAB. Diagn Cytopathol 1996; 15:185-190.

Background: The clinical significance of p53 suppressor gene nucleoprotein immunostaining in ovarian epithelial cancer has not been determined., Methods: p53 protein expression was studied by immunohistochemistry from paraffin embedded tissue in a series of 136 patients with malignant ovarian epithelial tumors. The median follow-up time of the patients still alive was 10 years., Results: Sixty (44%) carcinomas stained clearly positive for p53 protein. Positive staining for p53 protein was associated with the serous histologic type (P = 0.0006), a higher than the median S-phase fraction size determined by DNA flow cytometry (P = 0.02), and poor histologic grade of differentiation (P = 0.04), but not with the International Federation of Gynecology and Obstetrics (FIGO) stage, age at diagnosis, or DNA ploidy. Cancers with positive staining had only 17% 5-year and 9% 15-year survival rates compared with 42% 5-year and 36% 15-year survival rates corrected for intercurrent deaths among the rest of patients (P = 0.002). In a multivariate analysis, positive p53 staining was associated with poor survival (relative risk of death, 1.8, 95% confidence interval [CI], 1.2-2.9) together with less than radical surgery (nonradical vs. radical: RR, 5.5; 95% CI, 2.2-13.6), and advanced FIGO stage (RR, 1.4; 95% CI, 1.0-2.0)., Conclusion: Although p53 protein immunostaining is associated with several other prognostic factors in epithelial ovarian cancer, it may also have independent prognostic value in this disease.

The usefulness of fine-needle aspiration cytology (FNAC) in the diagnosis and treatment of submandibular gland lesions is not well known. The 210 FNACs taken from submandibular gland lesions at Turku University Central Hospital between 1984 and 1991 were reviewed. Of these FNACs, 78 samples from primary lesions were confirmed histologically. Within this subset 10 FNACs were taken from benign neoplasms, all of which were correctly classified (sensitivity 100 per cent; specificity 88 per cent). Only four of the 14 FNACs from malignant lesions were cytologically considered malignant (sensitivity 29 per cent). On the other hand, four FNACs raised a false suspicion of malignancy (specificity 6 per cent). Out of 54 FNACs from non-neoplastic lesions 43 were correct (sensitivity 80 per cent; specificity 63 per cent). There were 104 patients (123 FNACs), who had not been operated on: the follow-up of these patients shows that in this subset of FNACs there were no false malignant but probably one false benign finding (1 per cent). We conclude that FNAC can offer valuable information about the type of the submandibular gland lesion, but the decision of operative and other treatment should not be based solely on the result of FNAC.

In order to find out whether the response rate and survival in epithelial ovarian cancer can be improved by aid of sensitivity testing with the subrenal capsule assay (SRCA), 196 patients with FIGO Stage II-IV epithelial ovarian cancer were randomized to be treated with either cyclophosphamide-doxorubicin-cisplatin (CAP) or SRCA-guided chemotherapy. The drug combinations tested with the SRCA were (1) cyclophosphamide-doxorubicin-carboplatin (CACAR), (2) CAP, (3) carboquone-methotrexate-tegafur (CQ-MTX-TEG), (4) cisplatin-etoposide-hexamethyl-melamine (P-VP-HXM), and (5) bleomycin-epirubicin-cisplatin (BEP). A total of 132 patients (CAP, 69; SRCA, 63) were eligible for efficacy analysis based on relaparotomy findings. The overall response rate was 59% in the CAP arm and 62% in the SRCA arm. In the SRCA arm, 16 patients were treated with CACAR, 24 with CAP, 10 with CQ-MTX-TEG, 11 with P-VP-HXM, and 2 with BEP. The response rate to CACAR was 63% and to SRCA-CAP was 75%. The number of complete responses was higher when CAP was given as guided by the assay than when given at random (14/24 vs 23/69; P = 0.03, Pearson chi 2). Survival curves as estimated by Kaplan-Meier method gave a median survival of 24 (SE = 4) months to the SRCA arm and 28 (SE = 5) for the CAP arm (P = 0.7; log-rank test). Because no survival benefit was achieved, the SRCA obviously needs further development before it can be routinely recommended in the choice of first-line chemotherapy for patients with ovarian cancer.

Endometrial brush samples were taken from 1042 symptomatic hospital patients using Uterobrush(R), and the results were compared either to the histology of the endometrium obtained with dilatation and curettage (n = 313) or the patients' follow-up (n = 729). Only one cancer (100%) among patients 51 years of age (n = 365), 11 (91.7%) were detected by Papanicolaou classes III-V. One cancer was missed, whereas no false positive results were found. The diagnostic accuracy in this group of patients varied from 92.3% to 97.8%, depending on the group (true positive vs true negative) to which the Papanicolaou class III was placed. We conclude that endometrial cytology obtained by brushing is useful for symptomatic patients of all age groups and gives an indication for further examination. If cytology is normal and bleeding continues in postmenopausal patients, curettage is indicated.

The occurrence of abnormal nuclear DNA content in major salivary gland adenomas is not well known and its correlation with tumor recurrence has not been documented previously. From 1987 to 1991, 119 consecutive major salivary gland adenomas were operated on at Turku University Central Hospital. These tumors were analyzed by flow cytometry and 100 (84%) were found to be diploid, 12 (10%) near-diploid and 7 (6%) aneuploid with DNA indexes > 1.15. The mean proliferation rate measured as a percentage of cells in the S-phase fraction was 2.5 +/- 1.6%. The histological slides were then blindly reclassified according to current World Health Organization classification. As a result histological classification was changed in 3 tumors: malignant cells were found in 2 aneuploid tumors and 1 diploid neoplasm. Preoperative cytological fine-needle aspiration biopsy had been considered as possibly malignant in 2 of these cases. Among all case material 10 specimens were recurrent tumors; although the tendency to recur depended on the extent and adequacy of the surgery performed, multiple recurrences were associated with non-diploid tumors.

The methods most often used for follow-up of ovarian cancer are physical examination, CA-125 measurement and ultrasonography or computed tomography. In the present study the role of cul-de-sac aspiration cytology as a supplementary method was evaluated. We analyzed the records of 110 stage I-IV ovarian cancer patients who had undergone cul-de-sac aspiration as a part of their follow-up schedule after the primary treatment. During the median follow-up of 5 years altogether 577 cul-de-sac aspirations were performed with a median interval of 9 months. Only in 2 cases the obtained sample was insufficient for evaluation. Twenty patients had cul-de-sac cytology > or = class III at some point during the follow-up. In 12 cases the preceding or subsequent CA-125 values taken within 3 months were < 35 U/l. In 7 cases CA-125 values increased later, but in 5 cases the tumour marker values remained within normal range during the entire follow-up. Nine out of these 12 patients had a clinical recurrence later on, but 3 patients had no evidence of the disease. Twenty-seven recurrences were detected during the follow-up. Cul-de-sac aspiration cytology was the first or the only indication of recurrence in 9 cases (33%) and is a useful supplementary method in the follow-up of ovarian cancer.

Forty-nine follicular adenomas and 11 follicular carcinomas of the thyroid were investigated by immunohistochemistry for the expression of p53 protein and proliferating cell nuclear antigen (PCNA). The DNA ploidy and the S-phase fraction (SPF) of the neoplasms were analysed by flow cytometry. Twelve adenomas (24 per cent) and six carcinomas (55 per cent) were DNA non-diploid (P = 0.07). The carcinomas had a higher proliferation rate than the adenomas when assessed either by SPF size (median 9.9 per cent vs. 2.9 per cent, P = 0.0003) or by PCNA staining intensity (P < 0.0001). Some scattered nuclei in two (4 per cent) adenomas and in three (27 per cent) carcinomas stained positively for p53 (P = 0.04). The two adenomas with positive staining for p53 were subserially sectioned, but no signs of invasion were found; both patients are alive and well 6 and 7 years after surgery. One of the two adenomas showing positive p53 nuclear staining was DNA aneuploid, and both were positive in PCNA staining, but their SPFs were low (2.1 and 3.3 per cent). We conclude that p53 protein expression is not confined to follicular carcinomas; scattered p53-positive cells may also be present in histologically and clinically benign follicular adenomas. Because both follicular adenomas and carcinomas may be DNA aneuploid and their SPF and PCNA staining distributions overlap, the distinction between follicular adenoma and carcinoma should still be based on histological criteria.

The p53 suppressor gene protein expression was studied with immunoperoxidase staining in 61 serous tumors of the ovary. Twenty four (53%) of the 45 histologically malignant tumors were positive for p53, whereas neither the six benign nor the 10 tumors of borderline malignancy showed positive staining, except for one borderline tumor with atypia and increased mitotic activity. Therefore, p53 immunostaining may have diagnostic value in discriminating between borderline and malignant serous ovarian tumors. Malignant ovarian tumors with negative staining for p53 were associated with a 67% 3-year crude survival rate as compared with only an 18% 3-year survival rate if p53 staining was positive (p = 0.002). In a multivariate analysis, the p53 staining was the most important prognostic factor, with a relative risk of 4.2 (95% confidence interval, 1.8-9.9) followed by the FIGO stage (2.1, 1.3-3.5). We conclude that immunohistochemical p53 suppressor gene protein expression analysis has both diagnostic and prognostic value.

Three rare epithelial ovarian tumours, one malignant Brenner tumour, one transitional cell carcinoma and one Brenner tumour of borderline malignancy, are presented with special emphasis on the diagnostic, prognostic and therapeutic modalities. Because the prognosis of transitional cell carcinoma of the ovary is worse, as in our case, than that of the malignant Brenner tumour, this classification is justified.

Basal cell adenocarcinoma is a rare salivary gland tumour. A DNA diploid parotid gland basal cell adenocarcinoma, with a low mitotic rate, in a 78-year-old female patient is described. Total removal of the affected salivary gland without sacrificing the facial nerve gave a good therapeutic result.

To investigate the clinical significance of CD44 expression (lymphocyte-homing receptor) in adenocarcinoma, deparaffinized sections from 198 female breast carcinomas were stained with Hermes-3 MoAb for CD44 glycoprotein. In 16% of the cancers most (> or = 90%) of the cancer cells stained positively for CD44, whereas the rest of the cancers were either heterogenous (46%) or negative (38%) in CD44 staining. Cancers with > 50% CD44 positive cells were more often poorly differentiated (grade 3) than those with < or = 50% positive cells (38 vs. 19%, P = 0.006), they had higher mitotic counts (P = 0.04), and were more often estrogen receptor negative (52 vs. 31%, P = 0.01). Among ductal not otherwise specified cancers and node-positive cancers strong CD44 expression was associated with poor outcome (P = 0.05 and 0.02, respectively). However, CD44 expression was not an independent prognostic factor in these subgroups in a multivariate analysis. Unlike in lymphomas the unfavorable prognosis associated with CD44 expression may not be explained by the greater metastatic potential of CD44-positive cells, because the difference in mortality between the groups appeared to diminish with time, and CD44 positivity was associated with aggressive histological features.

DNA ploidy and S-phase fraction (SPF) of 69 lymphomas and 50 samples from benign lymphatic tissue were determined by flow cytometry from cells obtained by fine needle aspiration biopsy. An aneuploid histogram with a DNA index (DI) > 1.05 was obtained from 15 (22%) lymphomas. However, six (12%) benign lymph nodes also showed a bimodal DNA histogram, with the DI ranging from 1.06 to 1.15. The benign nature of these lymph nodes was confirmed by histology, follow-up of > 5 years or both. The median size of the SPF was 3.2%, 3.6%, 4.2%, 12.1% and 15.5% in benign lymph nodes, Hodgkin's disease and in low, intermediate and high grade non-Hodgkin's lymphomas, respectively. Only 8 (18%) of the benign tumors had an SPF > 5% as compared with 39 (62%) of the lymphomas (P < .0001). An SPF of > 12% was never obtained from benign tissue. The size of the SPF as determined from a fine needle aspirate correlates with lymphoma histology, and a bimodal DNA histogram with a small DI obtained from lymphatic tissue does not necessarily indicate the presence of lymphatic malignancy.

Objective: The purpose of this investigation was to evaluate the capability of ultra-low field MRI for staging endometrial carcinoma., Materials and Methods: Computed tomography and MRI were performed on 47 patients with uterine endometrial carcinoma. The results were compared with those from clinical examination and with histopathological results after operation in 43 cases. The local extension of the endometrial carcinoma was correctly staged in 77% with clinical examination in 58% with CT, and in 88% with MRI., Results: Tumor growth was overestimated by clinical examination in 21%, by CT in 35%, and by MRI in only 5%. Magnetic resonance imaging was most accurate in detecting cervical extension and was better than CT in detecting tumor invasion to the outer half of the myometrium. The sensitivities of CT and MRI in the assessment of deep myometrial invasion were 67 and 83%, respectively, the corresponding specificities being 67 and 79%. Magnetic resonance imaging at 0.02 T was not able to differentiate tumors with superficial myometrial invasion from those confined entirely to the endometrium. The detection of metastatic lymphadenopathy was difficult with all examination methods., Conclusion: Our results indicate that MRI at 0.02 T is a convenient, inexpensive, and accurate imaging method for the preoperative staging of endometrial carcinoma.

Four significant complications of Teflon injections for stress urinary incontinence are reported in 22 women and eight men. Three of the complications included periurethral abscess, urethral diverticulum, and periurethral Teflon granuloma with urethral wall prolapse occurred in women. These complications needed surgical excision and further surgery for stress incontinence, in two patients the outcome was good. Among the female patients the cure rate for stress incontinence with Teflon injection was only 18% in the 5-year follow-up. One other complication, a Teflon cyst, occurred in a male who had previously undergone radical retropubic prostatectomy. Only two of the eight men (25%) who received Teflon injections had maintained improvement after 1 year.

DNA ploidy, S-phase fraction (SPF), mitotic index (MI), volume corrected mitotic index (M/V index) and standard prognostic factors were related to disease outcome in a series of 363 women with breast cancer followed-up for over 10 years in our clinic. DNA ploidy and SPF were significantly related to histological type, tumour grade and mitotic indices (p < 0.001). In univariate survival analysis, pN status (p < 0.0001), tumour diameter (p < 0.0001), MI (p = 0.001), M/V index (p = 0.0003) and SPF (p = 0.015) predicted survival. In pN(-) tumours. MI (p = 0.059) was related to survival. In pN(+) tumours, tumour diameter (p = 0.0004), M/V index (p = 0.023) and SPF (p = 0.045) predicted survival. In multivariate survival analysis, tumour diameter (p < 0.001). M/V index (p < 0.007), pN status (p = 0.014) and patient age (p = 0.09) were independently related to survival. In pN(-) tumours, tumour diameter independently predicted survival (p = 0.033). In pN(+) tumours, tumour diameter (p < 0.001), M/V index (p = 0.006) and the year of treatment (p = 0.08) were independent predictors. The results show that tumour diameter, pN status and proliferative activity of cancer cells are important prognostic factors in breast cancer. Of the proliferation indices, M/V index and SPF are equally powerful predictors, and the use of M/V index is advocated due to simplicity of the assessment.

S phase fraction (SPF) and DNA ploidy were related to disease outcome by a separate analysis of sex steroid receptor positive and negative tumours in a series of 232 patients with breast carcinoma followed-up for over 8 years in our clinic. SPF was significantly higher in receptor-negative tumours than in receptor-positive ones (p = 0.037). SPF predicted recurrence only in ER+ or PR+ patients (p = 0.02-0.003). Recurrence-free survival (RFS) was significantly related to SPF only in ER+ (p = 0.001) and PR+ (p less than 0.001) tumours. In survival analysis, ER+ (p = 0.002) and PR+ (p less than 0.001) patients were efficiently divided into prognostic groups by SPF, whereas in ER- and in PR- tumours SPF had only suggestive predictive value. In N- tumours, SPF predicted recurrence-free survival and disease-related survival in ER+ (p = 0.003) (p = 0.039) and in PR+ (p = 0.003) (p = 0.012) tumours, respectively, whereas in ER-, PR-, tumours, SPF had no predictive value. In pN+ tumours, SPF also predicted survival in ER+ (p = 0.03) and in PR+ (p = 0.024) tumours. Thus the prognosis of ER+ or PR+ tumours with an SPF less than 9% is favourable with a risk of death of about 20%, in contrast to that of about 70% in tumours with an SPF greater than 9% during the follow-up period. To conclude, the proliferation rate as measured by S phase fraction by FCM is a highly significant prognostic factor in breast cancer. The prognostic value of S phase fraction is confined to steroid receptor-positive tumours, whereas in receptor-negative tumours SPF has no predictive value. The results thus suggest that all women with steroid receptor-negative breast tumours and those receptor-positive tumours with an SPF higher than 9% should be subjected to postoperative adjuvant chemotherapy immediately.

Objective: To examine how breast cancers found by mammographic screening differ from those found outside screening., Design: Comparative cohort study., Setting: Turku, southwestern Finland., Patients: 126 women aged 40-74 years with breast cancer detected during the first round of mammographic screening in 1987-90 and 125 women within the same age range with breast cancer detected outside screening during the same period., Main Outcome Measures: Primary tumour size, axillary nodal status, histological features, oestrogen and progesterone receptor concentrations, ploidy, and S phase fraction., Results: Compared with the controls women with cancers detected by screening had a smaller primary tumour (57 (46%) screened v 11 (10%) controls had tumours less than or equal to 11 mm in diameter, p less than 0.0001), and less often had axillary nodal metastases (104 (83%) screened v 71 (57%) controls node negative, p less than 0.0001). After adjustment for the smaller size of the primary tumour compared with control cancers, those cancers detected by screening were less likely to have axillary nodal metastases (odds ratio 0.44, 95% confidence interval 0.23 to 0.84), poor histological differentiation (0.20, 0.08 to 0.49), high mitotic counts (0.38, 0.15 to 0.97), tumour necrosis (0.45, 0.22 to 0.93) or to be of the ductal histological type (0.46, 0.22 to 0.95). They had low oestrogen receptor (0.29, 0.12 to 0.70) and progesterone receptor (0.35, 0.17 to 0.92) concentrations less often and had smaller S phase fractions (0.72, 0.55 to 0.96) than control cancers., Conclusions: Even after adjustment for the smaller size of screen detected breast cancers, their histological and cytometric features suggest low malignant potential. They may also be less likely to metastasise to axillary lymph nodes than cancers found outside screening.

The prognostic value of S-phase fraction (SPF) determined by flow cytometry from a fine-needle aspirate was investigated in a prospective series of 52 non-Hodgkin lymphomas. The aspirates were drawn either at diagnosis (n = 16) or at lymphoma recurrence (n = 36). Patients with lymphoma with a large SPF (> 10%, n = 24) had only a 21% 3-year survival rate corrected for intercurrent deaths as calculated from the date of aspiration, whereas a smaller SPF was associated with a 71% 3-year survival rate (n = 28, P = 0.0009). SPF size also correlated with Working Formulation grading (P = 0.002). In a multivariate analysis the relative risk of death from lymphomas with a large SPF was 4.01 (1.60-10.1), whereas histological grading, age, and sex had no additional independent prognostic value. SPF determined from a fine needle aspirate had unexpectedly good prognostic value, and the result suggests that the method is of clinical importance.

Eighteen pancreatic neuroendocrine (NE) tumours were analysed for nuclear DNA content by image cytometry (ICM) and flow cytometry (FCM). The DNA indices (DIs) obtained by ICM were somewhat higher than those obtained by FCM, but a major disagreement was present only in 1 case. Thirteen patients had been followed up at least for 6 years after the diagnosis or until death. At 6 years of follow-up all 4 patients with a tumour with a DI greater than or equal to 1.8 by ICM had died from their NE tumour or had metastatic disease, whereas all 9 patients with a smaller DI had no evidence of the disease (P = 0.001). The DIs calculated from the FCM data also correlated well with the final outcome (P = 0.01). A high incidence of DNA aneuploidy was found by both methods in histologically and clinically benign NE tumours; 12 (67%) were DNA aneuploid by FCM and 16 (89%) by ICM. It is concluded that pancreatic NE tumours are frequently DNA aneuploid, and both cytometric DNA methods give prognostic information in these tumours. The presence of DNA aneuploidy should not be considered as a sign of malignant behaviour in pancreatic NE tumours, whereas a large DI is associated with poor prognosis.

The prognostic value of S-phase fraction (SPF), determined by flow cytometric study from paraffin-embedded tissue, and grading by Working Formulation (WF) and Kiel classification were compared among 245 patients with non-Hodgkin's lymphoma followed for the median of 89 months or until death. Histologic reclassification and SPF determinations were done without knowledge on clinical data. SPF (P equals 0.0001), WF (P equals 0.0003), and Kiel classification (P equals 0.0008) were associated with mortality in lymphoma in a univariate analysis, and WF and SPF were independent prognostic factors in Cox's multivariate analysis. Although SPF correlated strongly both with WF and Kiel grades (P less than 0.0001), low-grade and high-grade malignant lymphomas according to Kiel classification, and high-grade lymphomas according to WF could be divided into groups with significantly different outcome by SPF. The results suggests a role for SPF in therapeutic decision-making.

The fine needle aspiration (FNA) biopsies performed on thyroid nodules at Turku University Central Hospital from 1983 to 1988 were reviewed. Of the 1,054 total aspirated nodules, 194 were investigated histologically after thyroid surgery (191 cases) or at autopsy (3 cases). Two cases with an insufficient FNA sample, 4 with an incidental occult papillary carcinoma and 2 cases with carcinoma outside the nodule investigated by FNA biopsy were excluded from the series, leaving 186 histologically confirmed nodules in the final analysis. Three (3%) of the 107 cases with an FNA biopsy diagnosis of benign, 4 (8%) of the 52 with an FNA diagnosis of equivocal, 3 (20%) of the 15 with an FNA diagnosis of suspicious and all 12 (100%) with an FNA diagnosis of malignant were histologically malignant. If only an unequivocally malignant cytologic finding is considered positive, FNA biopsy had a diagnostic specificity of 100%, a sensitivity of 55% and an accuracy of 95% among the histologically confirmed cases. Follow-up revealed no cases of cancer among the 863 thyroids that were not explored surgically. It is concluded that FNA biopsy is a practical method with considerable diagnostic value in the evaluation of thyroid nodules.

The effects of toremifene, a new antiestrogenic drug, were investigated in vitro on the exponentially growing human mammary carcinoma cell line MCF-7. The drug effects were monitored by serial cell counts and DNA flow cytometry. The inhibitory effect of toremifene on MCF-7 became greater as the drug concentration was increased from 1 microM to 10 microM. At 5 microM toremifene induced a large decrease in the relative percentages of S- and G2/M-phase cells, and an increase in the amount of cell debris, indicating increased cell death. After withdrawal of the drug the mammary cancer cells resumed logarithmic growth similar to that of control cells. The effects caused by toremifene were similar to those caused by tamoxifen both in quality and quantity.

The prognostic significance of DNA ploidy, DNA index (DI), and S-phase fraction (SPF) and their various combinations were studied together with 16 other clinicopathologic factors in 222 patients with operable invasive ductal breast carcinoma. The patients have been followed for a minimum of 22 years after the diagnosis or until death. Nuclear DNA content was determined by flow cytometry from paraffin-embedded tissue. Patients with DNA diploid cancer (n = 57, 26%) had better survival rate corrected for intercurrent deaths than patients with nondiploid cancer (P = 0.002), and also, a small SPF (less than or equal to 14%, calculated in 134 cases) was associated with a favorable outcome in a univariate analysis (P = 0.01). The prognostic value of the DI and SPF was increased if they were combined. The most effective combination was obtained if diploid cancers were grouped together with DNA aneuploid cancers with a DI less than 2.1 and an SPF less than 14%. This combination had considerable prognostic value in a univariate analysis (P = 0.0002) and had independent prognostic value (P = 0.04) in Cox's multivariate analysis together with the primary tumor size (P less than 0.001) in axillary node negative patients but not in axillary node positive patients. In the whole series the presence of axillary nodal metastases (P less than 0.001), high mitotic count (P less than 0.001), a large primary tumor size (P = 0.001), poorly circumscribed tumor margin (P = 0.005), and slight or absent tubule formation (P = 0.05) were the only independent prognostic factors in a multivariate analysis.

The nuclear DNA content of 37 primary non-Hodgkin's lymphomas both at presentation and at relapse was determined by flow cytometric analysis from paraffin-embedded tissue to investigate changes in DNA ploidy and S-phase fraction (SPF) during the course of the disease, and their association with survival. The repeat biopsies were done from 5 months to 15 years after the diagnosis. Four low-grade lymphomas according to the Working Formulation transformed into intermediate-grade lymphomas (four of 11, 36%), and four intermediate-grade lymphomas into high-grade lymphomas during the follow-up (four of 16, 25%), and five of these eight transformed lymphomas were fatal within 18 months after relapse. The SPF correlated strongly with poor prognosis if measured either from the primary biopsy (P = 0.008), the first (P = 0.009), or the latest repeat biopsy (P = 0.006). If SPF was greater than or equal to 6% larger in a repeat biopsy than at presentation prognosis was poor; six of nine such patients died from lymphoma within 11 months from recurrence. An increase of greater than or equal to 6% in the SPF was more common in high-grade (four of nine, 44%) and intermediate-grade (four of 16, 25%) lymphomas than in low-grade lymphomas (one of 11, 9%), and it was occasionally (three of nine) associated with a morphologic change. In a few cases a repeat biopsy was diploid despite DNA aneuploidy at presentation. In conclusion, the study provides evidence that not only may low-grade lymphomas transform into higher grade lymphomas, but high-grade lymphomas may also frequently transform into more malignant forms during the course of the disease. The SPF is useful in monitoring the biological behavior of non-Hodgkin's lymphoma, and it appears to give information not obtained by histologic study alone.

The nuclear DNA content of 17 pancreatic neuroendocrine tumors was measured from paraffin-embedded tissue with flow cytometry. The tumors were classified by immunostaining with antisera for synaptophysin, insulin, gastrin, glucagon, pancreatic polypeptide, somatostatin, and vasoactive intestinal polypeptide. Eight (47%) of the 17 tumors were aneuploid, and two (12%) were multiploid (had two aneuploid stemlines of cells). Seven of the eight insulinomas, one of the four gastrinomas, and two of the four nonspecified neuroendocrine tumors had an abnormal nuclear DNA content. The DNA indices of the aneuploid and multiploid cases ranged from 1.13 to 1.93, and three cases had a DNA index greater than 1.50. During the follow-up for up to 16 years (mean, 7 years), one patient with diploid nonspecified tumor died of the disease, another patient with a multiploid gastrinoma had metastatic disease develop, and a third patient with a multiploid nonspecified tumor was alive with the disease. The authors conclude that many neuroendocrine tumors of the pancreas have an abnormal nuclear DNA content as measured by DNA flow cytometry. DNA multiploid pancreatic neuroendocrine tumors may be associated with a less favorable clinical course, but this needs to be confirmed in additional studies.

The nuclear DNA content of 62 pancreatic adenocarcinomas was analysed by flow cytometry from paraffin-embedded material. Radical surgery could be performed in 12 of the 24 cases with diploid carcinoma, but only in 3 of the 38 cases with a non-diploid tumour (P = 0.0002); the radically resected carcinomas also had a lower fraction of cells in the S-phase (P = 0.009). Non-diploid nuclear DNA content (38 cases, 61 per cent) was associated with advanced stage (P = 0.002), poor histological differentiation (grade II or III, P = 0.004), and primary tumour site in the body or the tail as compared with the head (P = 0.01). The median survival time of the patients with diploid carcinoma was 13 +/- 3 (SE) months, and that of the patients with non-diploid carcinoma 3 +/- 1 months (P = 0.0001). The DNA index with the cutoff value 1.4 was a slightly more powerful prognostic factor than DNA ploidy, and it was the most important independent prognostic factor in Cox's multivariate analysis (P less than 0.001) followed by histological grade (P less than 0.03). We conclude that diploid pancreatic carcinomas are associated with a longer survival than the non-diploid ones, and that radically operable carcinomas form a special subgroup with frequent diploidy and less aggressive biological behaviour.